• Title/Summary/Keyword: Resistant model

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miR-335 Targets SIAH2 and Confers Sensitivity to Anti-Cancer Drugs by Increasing the Expression of HDAC3

  • Kim, Youngmi;Kim, Hyuna;Park, Deokbum;Jeoung, Dooil
    • Molecules and Cells
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    • v.38 no.6
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    • pp.562-572
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    • 2015
  • We previously reported the role of histone deacetylase 3 (HDAC3) in response to anti-cancer drugs. The decreased expression of HDAC3 in anti-cancer drug-resistant cancer cell line is responsible for the resistance to anti-cancer drugs. In this study, we investigated molecular mechanisms associated with regulation of HDAC3 expression. MG132, an inhibitor of proteasomal degradation, induced the expression of HDAC3 in various anti-cancer drug-resistant cancer cell lines. Ubiquitination of HDAC3 was observed in various anti-cancer drug-resistant cancer cell lines. HDAC3 showed an interaction with SIAH2, an ubiquitin E3 ligase, that has increased expression in various anti-cancer drug-resistant cancer cell lines. miRNA array analysis showed the decreased expression of miR-335 in these cells. Targetscan analysis predicted the binding of miR-335 to the 3'-UTR of SIAH2. miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR-335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs.

The Study of Antibiotic Resistance in Bacterial Biofilms (박테리아 생체막에 대한 항생제 내성 연구)

  • Kim Jin Wook;Joo Chi Un;Park Jin Yong;Lee Song Ae;Kim In Hae;Lee Jae Hwa
    • Environmental Mutagens and Carcinogens
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    • v.25 no.4
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    • pp.157-160
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    • 2005
  • Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infection and disease. The penetration of antibiotic, through biofilm developed in an itt vitro model system was investigated. Antibiotic resistant bacteria (E. coli) were obtained from Culture Collection of Antibiotic Resistant Microbes. Ca-alginate bead used as simulated biofilm and a cell entrapment test using compressed air were experiment for the improvement cell viability. Antibiotic susceptibilities though biofilms was measured by assaying the concentration of antibiotic that diffused through the biofilm to minimal inhibition concentration (MIC). Survival of immobilized cells were reduced as compared to free cells. In case of antibiotic susceptible E. coli reduced continuously, but antibiotic resistant E. coli kept up survival rate constantly. Survival was showed after exposed to the antibiotics that the more treated antibiotic resistant E. coli and low concentration of antibiotics) the more survived.

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Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells

  • Seung-On Lee;Mee-Hyun Lee;Ah-Won Kwak;Jin-Young Lee;Goo Yoon;Sang Hoon Joo;Yung Hyun Choi;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • v.31 no.6
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    • pp.661-673
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    • 2023
  • Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

Coupled testing-modeling approach to ultimate state computation of steel structure with connections for statics and dynamics

  • Imamovic, Ismar;Ibrahimbegovic, Adnan;Mesic, Esad
    • Coupled systems mechanics
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    • v.7 no.5
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    • pp.555-581
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    • 2018
  • The moment-resistant steel frames are frequently used as a load-bearing structure of buildings. Global response of a moment-resistant frame structure strongly depends on connections behavior, which can significantly influence the response and load-bearing capacity of a steel frame structure. The analysis of a steel frame with included joints behavior is the main focus of this work. In particular, we analyze the behavior of two connection types through experimental tests, and we propose numerical beam model capable of representing connection behavior. The six experimental tests, under monotonic and cyclic loading, are performed for two different types of structural connections: end plate connection with an extended plate and end plate connection. The proposed damage-plasticity model of Reissner beam is able to capture both hardening and softening response under monotonic and cyclic loading. This model has 18 constitutive parameters, whose identification requires an elaborate procedure, which we illustrate in this work. We also present appropriate loading program and arrangement of measuring equipment, which is crucial for successful identification of constitutive parameters. Finally, throughout several practical examples, we illustrate that the steel structure connections are very important for correct prediction of the global steel frame structure response.

Stress path adapting Strut-and-Tie models in cracked and uncracked R.C. elements

  • Biondini, Fabio;Bontempi, Franco;Malerba, Pier Giorgio
    • Structural Engineering and Mechanics
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    • v.12 no.6
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    • pp.685-698
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    • 2001
  • In this paper, a general method for the automatic search for Strut-and-Tie (S&T) models representative of possible resistant mechanisms in reinforced concrete elements is proposed. The representativeness criterion here adopted is inspired to the principle of minimum strain energy and requires the consistency of the model with a reference stress field. In particular, a highly indeterminate pin-jointed framework of a given layout is generated within the assigned geometry of the concrete element and an optimum truss is found by the minimisation of a suitable objective function. Such a function allows us to search the optimum truss according to a reference stress field deduced through a F.E.A. and assumed as representative of the given continuum. The theoretical principles and the mathematical formulation of the method are firstly explained; the search for a S&T model suitable for the design of a deep beam shows the method capability in handling the reference stress path. Finally, since the analysis may consider the structure as linear-elastic or cracked and non-linear in both the component materials, it is shown how the proposed procedure allows us to verify the possibilities of activation of the design model, oriented to the serviceability condition and deduced in the linear elastic field, by following the evolution of the resistant mechanisms in the cracked non-linear field up to the structural failure.

Differential Privacy Technology Resistant to the Model Inversion Attack in AI Environments (AI 환경에서 모델 전도 공격에 안전한 차분 프라이버시 기술)

  • Park, Cheollhee;Hong, Dowon
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.29 no.3
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    • pp.589-598
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    • 2019
  • The amount of digital data a is explosively growing, and these data have large potential values. Countries and companies are creating various added values from vast amounts of data, and are making a lot of investments in data analysis techniques. The privacy problem that occurs in data analysis is a major factor that hinders data utilization. Recently, as privacy violation attacks on neural network models have been proposed. researches on artificial neural network technology that preserves privacy is required. Therefore, various privacy preserving artificial neural network technologies have been studied in the field of differential privacy that ensures strict privacy. However, there are problems that the balance between the accuracy of the neural network model and the privacy budget is not appropriate. In this paper, we study differential privacy techniques that preserve the performance of a model within a given privacy budget and is resistant to model inversion attacks. Also, we analyze the resistance of model inversion attack according to privacy preservation strength.

Overcoming multidrug resistance by activating unfolded protein response of the endoplasmic reticulum in cisplatin-resistant A2780/CisR ovarian cancer cells

  • Jung, Euitaek;Koh, Dongsoo;Lim, Yoongho;Shin, Soon Young;Lee, Young Han
    • BMB Reports
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    • v.53 no.2
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    • pp.88-93
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    • 2020
  • Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

Expression in Successive Generations of bar Gene Introduced in Petunia (Petunia에 도입된 bar Gene의 세대진전에 따른 발현 양상)

  • Ha, Young-Min;Park, Sang-Mi;Kim, Zhoo-Hyeon
    • Journal of Plant Biotechnology
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    • v.31 no.4
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    • pp.261-266
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    • 2004
  • This experiment was carried out to confirm the stability of bar gene introduced into petunia plant through Agrobacterium-mediated transformation, in successive generation, or after crossing or back-crossing. Some of different 25 transgenic plants were used in crossing and back-crossing to wild type, or repeated-selfing to T$_4$ generation. On the processing of experiment, it was found that some lines lost their resistant ability to herbicide basta, or showed non-Mendelian segregation mode: produced much more susceptible segregants than resistant plants. Even though there are exceptional cases, which was off from expected, the genetic stability of bar gene introduced could be confirmed strongly, because in almost case, the segregation of resistant and susceptible plants to basta was done under Mendelian-law according to single gene dominant model.

Structural Analysis of Impact·Blast Resistant Composite Panel using ACP and AUTODYN (ACP와 AUTODYN을 이용한 방호·방폭 보강 복합패널 구조해석)

  • Kim, Woonhak;Kang, Seokwon
    • Journal of the Society of Disaster Information
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    • v.12 no.4
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    • pp.432-439
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    • 2016
  • To make a model of a Impact/Blast resistant composite material and perform the analysis, material properties of the composite material are required. In order to obtain such a property value, it is necessary to input the result obtained by performing a lot of material tests by the calculation formula of the situation, and there is a lot of difficulty in the case of a special purpose material which is not a general material. In this study, modeling and structural analysis of composite fiber panels for protection and explosion - proofing were performed in ACP(ANSYS Composite PrePost) and AUTODYN by applying the application properties of composites provided in Ansys Workbench environment.

Isovitexin Protects Mice from Methicillin-Resistant Staphylococcus aureus-Induced Pneumonia by Targeting Sortase A

  • Tian, Lili;Wu, Xinliang;Yu, Hangqian;Yang, Fengying;Sun, Jian;Zhou, Tiezhong;Jiang, Hong
    • Journal of Microbiology and Biotechnology
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    • v.32 no.10
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    • pp.1284-1291
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    • 2022
  • The rise of methicillin-resistant Staphylococcus aureus (MRSA) has resulted in significant morbidity and mortality, and clinical treatment of MRSA infections has become extremely difficult. Sortase A (SrtA), a virulence determinant that anchors numerous virulence-related proteins to the cell wall, is a prime druggable target against S. aureus infection due to its crucial role in the pathogenicity of S. aureus. Here, we demonstrate that isovitexin, an active ingredient derived from a variety of traditional Chinese medicines, can reversibly inhibit SrtA activity in vitrowith a low dose (IC50=24.72 ㎍/ml). Fluorescence quenching and molecular simulations proved the interaction between isovitexin and SrtA. Subsequent point mutation experiments further confirmed that the critical amino acid positions for SrtA binding to isovitexin were Ala-92, Ile-182, and Trp-197. In addition, isovitexin treatment dramatically reduced S. aureus invasion of A549 cells. This study shows that treatment with isovitexin could alleviate pathological injury and prolong the life span of mice in an S. aureus pneumonia model. According to our research, isovitexin represents a promising lead molecule for the creation of anti-S. aureus medicines or adjuncts.